Survival advantage of laparoscopic versus open resection for colorectal liver metastases: A patient-level meta-analysis of propensity-score-matched studies

Abstract

Background: Propensity-score matched (PSM) studies currently constitute the highest level of evidence in addressing the long-term oncologic efficacy of laparoscopic versus open resection for colorectal liver metastases (CLM). However, individual PSM studies are limited by the reporting of overall survival in ways not amenable to traditional methods of meta-analysis, as well as violation of the proportional hazards assumption. We performed an individual participant data (IPD) meta-analysis of overall survival based on PSM studies which compared laparoscopic versus open hepatectomy for patients with CLM. Materials and Methods: We searched EMBASE, Scopus and Medline for propensity-score matched studies without language restriction from inception to Dec 6, 2018. Overall survival information of individual participants were reconstructed from published Kaplan-Meier curves with the aid of a computer vision program. Survival models (taking into account random-effects, time-varying effects, and non-proportional hazards) were fitted to compare overall survival of patients who underwent laparoscopic versus open surgery. Results: Individual patient data from 10 propensity-score-matched studies involving 2,539 participants were reconstructed. Laparoscopic resection was associated with lower mortality over the entire duration of follow-up (stratified HR=0.831, 95% CI: 0.719-0.960, P=0.0120). There was evidence of time-varying effects (P=0.0212), and HRs were found to increase in magnitude over time: HR=0.991 [P=0.9320], HR=0.868 [P=0.0482], HR=0.804 [P=0.0026], HR=0.729 [P=0.0007], and HR=0.638 [P=0.0011] at 1, 2, 3, 5, and 10 years respectively. At 10- and 15-year follow-up, the restricted mean survival time (RMST) were 9.6 months and 32.3 months longer in the laparoscopic arm, corresponding to a 13.4% and 40.8% gain in RMST respectively (allP<0.0001). Conclusions: All analyses indicated a consistent survival benefit in favor of laparoscopic over open resection for CLM in the long-term. Mechanisms for the delayed divergence in survival curves, which emerges only after 2 years post-resection, warrant further research.